Technical Abstract:
In 2006 a unique syndrome with high morbidity and mortality was recognized in growing pigs in China that became known as porcine high fever disease (PHFD). One consistent finding in affected pigs was the detection of porcine reproductive and respiratory syndrome virus (PRRSV) that had unique nsp2 gene mutations. Experimental infection of pigs with these novel isolates reproduced the clinical disease providing strong evidence for the role of PRRSV as the causal agent of PHFD. However, there was still a question if there was some unknown agent in the PRRSV preparations that increased the severity of the clinical disease over what was expected for a "routine" PRRSV infection. This question was resolved when PHFD was reproduced with virus derived from an infectious clone of the JX143 PRRSV isolate. These studies demonstrated that PRRSV isolates with a common genetic motif had a causal role in PHFD leading to this lineage of virus being called highly pathogenic PRRSV (HP-PRRSV). We imported a plasmid containing a full-length clone of the JXwn06 HP-PRRSV isolate. Infectious virus (rJXwn06) was rescued from the clone and used to inoculate young pigs in a series of studies. All non-vaccinated pigs given the rJXwn06 virus developed a pronounced fever about 2 days post inoculation (dpi) followed by anorexia and listlessness in most pigs and vomiting in some. From about 5 dpi until the end of each experiment pigs became very sick developing respiratory distress, ataxia, cachexia, diarrhea, red-blue discoloration of extremities and many became moribund at which time the pigs were euthanized for humane purposes. In contrast, pigs given VR-2332 challenge virus were much less affected with a mild to moderate fever and no mortality. Vaccination with a commercially available vaccine attenuated the clinical effect of the rJXwn06 challenge when compared to non-vaccinated challenge controls. However, many of the vaccinated pigs became very sick following challenge but were recovering by the conclusion of the experiment. Control pigs appeared clinically normal in all experiments with no microscopic or macroscopic lung lesions. VR-2332 infected pigs developed lung lesions consistent with a PRRSV infection. Severe pneumonia was observed in most of the HP-PRRSV infected pigs. Bacteria were isolated from lung lavage of 9/40, 0/29, and 86/100 control, VR-2332, and HP-PRRSV infected pigs, respectively. Bordetella bronchiseptica and Haemophilus parasuis were the only bacteria isolated from the controls (6/9 from one experiment), whereas a wide variety of typical respiratory bacterial pathogens as well as less frequently isolated opportunists were isolated from the HP-PRRS infected group.
In summary, our studies with rJXwn06 virus are consistent with other HP-PRRSV reports. Based on our experience with experimental PRRSV infections, the HP-PRRSV isolate has a potent immunomodulating capacity that negatively affects the pig's homeostasis, this was most striking in some experiments that had 100% mortality in the HP-PRRSV group.